AB0035 FREQUENCY OF LYMPH NODE STROMAL CELLS HLA-DR+ IS REDUCED IN INGUINAL LYMPH NODES FROM HUMAN DONORS WITH RHEUMATOID ARTHRITIS COMPARED TO CONTROLS
Authors: C. Grasso
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid arthritis (RA) is an autoimmune disorder where the immune system gradually damages a wide variety of body systems, including the skin, eyes, lungs, heart, and blood vessels 1 . Animal studies have shown that lymph node stromal cells (LNSCs) are key players in peripheral tolerance through their capacity to present self-antigen to T cells thereby controlling auto reactivity and regulating autoimmunity and humoral response 4,5 . Although self-antigen presentation by human LNSCs needs to be formally proven in human, this study speculates that malfunctioning LNSCs might be associated with loss of tolerance in autoimmune diseases like RA. Objectives The objective of this study is to assesses and compare the frequency of main LNSC subsets in human lymph node needle biopsies of healthy controls, autoantibody positive individuals at risk of developing RA (RA-risk) and RA patients. We especially focussed on markers for antigen presentation expressed by LNSCs. Methods RA at risk, RA and healthy (n=1) participants underwent an ultrasound-guided inguinal LN needle core biopsy as previously described 6 . We included RA-risk participants (n = 6) with elevated IgM-RF and/or ACPA levels, but without any evidence of arthritis upon examination; RA patients (n =13) with established disease based on fulfilment of the American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) 2010 criteria as assessed by the rheumatologist. For comparison we included healthy participant (n = 17) The healthy control was without any joint complaints and without elevated IgM-RF and/or ACPA level and without active viral infection or any history of autoimmunity or malignancy. To increase the number of healthy participants in the control group, we included lymph node biopsies from individuals receiving a kidney transplant (n= 16). After collection, tissue samples were enzymatically digested to obtain a single cell suspension, followed by flowcytometry analysis with the following cell surface markers CD40, CD80, CD86, PD-L1, HLA-DR, CD45, PDPN, CD31, CD235a, Viability dye. Results Antigen presentation related co-stimulatory molecules (CD40, CD80, CD86, PD-L1) and HLA-DR were detected at low levels. Blood endothelial cells having the highest expression of HLA-DR followed by LECs, FRCs, DNs. WE observed a reduced frequency of HLA-DR+ lymph node stromal cell (CD45-, CD235a-) in RA and at RA at risk compared to control. After we found that FRCs, DNs, and BECs were reduced in RA and RA at risk compared to healthy control population. Conclusion Our findings show that the frequency of HLA-DR positive LNSCs is lower in RA-risk individuals and RA patients compared to controls. As HLA-DR is crucial to present self-antigens and promote self-tolerance, it will be of interest to investigate whether the antigen presenting capacity of LNSCs is diminished already before onset of disease and how we could restore this. Disclosure of Interests None declared